Phase II study of Vigil® DNA engineered immunotherapy as maintenance in advanced stage ovarian cancer

Gynecol Oncol. 2016 Dec;143(3):504-510. doi: 10.1016/j.ygyno.2016.09.018. Epub 2016 Sep 24.

Abstract

Objectives: The majority of women with Stage III/IV ovarian cancer who achieve clinical complete response with frontline standard of care will relapse within 2years. Vigil immunotherapy, a GMCSF/bi-shRNA furin DNA engineered autologous tumor cell (EATC) product, demonstrated safety and induction of circulating activated T-cells against autologous tumor in Phase I trial Senzer et al. (2012, 2013) . Our objectives for this study include evaluation of safety, immune response and recurrence free survival (RFS).

Methods: This is a Phase II crossover trial of Vigil (1.0×107 cells/intradermal injection/month for 4 to 12 doses) in Stage III/IV ovarian cancer patients achieving cCR (normal imaging, CA-125≤35units/ml, physical exam, and no symptoms suggestive of the presence of active disease) following primary surgical debulking and carboplatin/paclitaxel adjuvant or neoadjuvant chemotherapy. Patients received Vigil or standard of care during the maintenance period.

Results: Forty-two patients were entered into trial, 31 received Vigil and 11 received standard of care. No≥Grade 3 toxicity related to product was observed. A marked induction of circulating activated T-cell population was observed against individual, pre-processed autologous tumor in the Vigil arm as compared to pre-Vigil baseline using IFNγ ELISPOT response (30/31 negative ELISPOT pre Vigil to 31/31 positive ELISPOT post Vigil, median 134 spots). Moreover, in correlation with ELISPOT response, RFS from time of procurement was improved (mean 826days/median 604days in the Vigil arm from mean 481days/median 377days in the control arm, p=0.033).

Conclusion: In conjunction with the demonstrated safety, the high rate of induction of T-cell activation and correlation with improvement in RFS justify further Phase II/III assessment of Vigil.

Publication types

  • Clinical Trial, Phase II
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Cancer Vaccines / therapeutic use*
  • Carboplatin / administration & dosage
  • Carcinoma, Endometrioid / drug therapy*
  • Carcinoma, Endometrioid / pathology
  • Cross-Over Studies
  • Cytoreduction Surgical Procedures*
  • Disease-Free Survival
  • Female
  • Humans
  • Middle Aged
  • Neoadjuvant Therapy
  • Neoplasms, Cystic, Mucinous, and Serous / drug therapy*
  • Neoplasms, Cystic, Mucinous, and Serous / pathology
  • Ovarian Neoplasms / drug therapy*
  • Ovarian Neoplasms / pathology
  • Paclitaxel / administration & dosage
  • T-Lymphocytes

Substances

  • Cancer Vaccines
  • FANG vaccine
  • Carboplatin
  • Paclitaxel